Comparison of Fast-Progression, Hyperprogressive Disease, and Early Deaths in Advanced Non–Small-Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or Chemotherapy

Abstract

PURPOSE Hyperprogressive disease (HPD), fast progression (FP), and early death (ED) have been described in 13.8%, 4.7%, and 5.6% and in 5.1%, 2.8%, and 6.8%, respectively, of patients with non–small-cell lung cancer (NSCLC) treated with single-agent programmed cell death ligand 1 inhibitors (ICI) or chemotherapy, respectively. Whether FP/ED and HPD represent overlapping patterns is unknown. PATIENTS AND METHODS FP, ED, and HPD were retrospectively assessed in patients with NSCLC treated with single-agent ICI or chemotherapy. Eligibility required 2 computed tomography (CT) scans before and 1 CT scan during treatment. (1) HPD, (2) FP, (3) ED were defined as (1) RECIST version 1.1 progression at first CT scan and tumor growth rate variation per month > 50%, (2) ≥ 50% increase in the sum of the longest diameters of target lesions within 6 weeks from baseline, and (3) death as a result of radiologic progression within 12 weeks from baseline CT scan, respectively. RESULTS Of 406 ICI-treated NSCLC, 56 patients (13.8%), 9 patients (2.2%), and 36 patients (8.8%) were HPD, FP, and ED, respectively. Eight (14.2%) and 20 (35.7%) of 56 patients with HPD were also FP and ED. ED significantly correlated with baseline Eastern Cooperative Oncology Group performance status ≥ 2 compared with HPD (33% v 13%, P = .02). Overall survival was significantly longer for HPD (3.4 months [95% CI, 2.7 to 4.0 months]) compared with FP (0.7 months [95% CI, 0.6 to 0.8 months]); HR, 0.18 [95% CI, 0.08 to 0.42]; P < .0001) and ED (1.4 months [95% CI, 1.3 to 1.6 months]); HR, 0.19 [95% CI, 0.11 to 0.34]); P < .0001), whereas it did not differ between FP and ED (HR, 1.3 [95% CI, 0.56 to 3.0]; P = .55). Of 59 patients with NSCLC treated with single-agent chemotherapy, the HPD, FP, and ED rates were 5.1%, 1.7%, and 6.7%, respectively. CONCLUSION FP, ED, and HPD represent distinct progression patterns with limited overlap and different survival outcomes.

Longitudinal liquid biopsy anticipates hyperprogression and early death in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors

“…Among potential clinical criteria, we decided to include patients experiencing death within 12 weeks from the start of ICIs, being an objective criterion and a phenomenon already observed in several clinical trials [6,11]. Evidence about lack of complete overlap between the two phenomena, ED and HPD, in line with previous observations [23,24], has been confirmed in our experience. We also confirmed the potential impact of extrathoracic disease on the risk of developing ED or HPD and the occurrence of ED even in patients expressing high level of PD-L1 and treated in a first-line setting [3,10,25].…”

Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics

“…Biomarkers to predict these aggressive patterns are currently a major need for patients on ICI therapy. While, in lung cancer, high-dNLR at baseline was not initially associated with HPD [33], Kim et al recently reported that high-dNLR (>4) was independently associated with HPD (differently defined). We observed, using dNLR score, that 12-week death rate was higher in high-dNLR (B) population (27% vs. 15% overall), and increased up to 32% if continued high-dNLR, supporting the biological hypothesis of neutrophil involvement on ICI resistance [12].…”

Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors

“…Hyperprogressive disease (HPD) refers to cases that the volume of the tumor lesion does not decrease but increases after immunotherapy, with a faster disease progression (typically at least two times) compared to before treatment [133,134]. HPD induced by PD-1 inhibitor immunotherapy is another challenge for immunotherapy alone in addition to their low response rate.…”